In cerebral cortex, horizontal connections link cells with their near neighbors and with neurons millimeters apart. While previous anatomical and physiological studies have suggested that long-range horizontal connections do not contribute to basic response tuning properties but instead serve to modulate these responses, it is possible that the more numerous short-range horizontal connections actually participate in sensory response tuning. Here, we propose experiments to investigate the role of short-range horizontal connections in cortical computations. In the first set of experiments, we will record the activity of dozens of closely-spaced layer 2/3 neurons using two-photon imaging of calcium dye to characterize fine scale organization of retinotopic and orientation maps. In addition to serving as a baseline for manipulations of short-range horizontal connections, we will study the interactions between the mapping of retinotopic location and orientation selectivity to see if functional parameters are mapped independently or if abrupt changes in one mapped parameter correlate with abrupt changes in another parameter. In our second and third sets of experiments, we will study the influence of short-range horizontal connections by manipulating activity of small groups of neurons and re-measuring retinotopic location and orientation selectivity in neighboring cells. In Aim 2, we will reduce activity in some layer 2/3 cells by stimulus adaptation with high contrast, oriented drifting gratings. In Aim 3, we will inactivate or stimulate small groups of neurons with microintophoresis of either GABA or glutamate. If short-range horizontal connections play a role in basic response tuning properties, we would expect to see shifts in receptive field location or orientation preferences. These tuning preferences should shift away from the preferences of inactivated cells and should shift towards preferences of stimulated cells. Two-photon calcium imaging will allow us to 1) record activity of immediate neighbors to manipulated cells, 2) directly monitor the extent of our manipulations, and 3) examine the dependence of response shifts on distance. Our long-term goals are to understand principles of cortical organization and cellular mechanisms underlying visual responses in the mammalian visual system. The experiments we propose here will build the foundation for attaining this goal. This knowledge will provide key insights into the normal function of the human visual system that will be useful for understanding the impact of disease or injury on cortical function, such as the developmental disease amblyopia, stroke, or cortical reorganization following retinal lesions. [unreadable] [unreadable] [unreadable]